WHAT IS CANCER?

Our video series includes animations describing the biological processes that are involved with cancer. This interface takes a serial approach for adequately describing all the complicated cancer biology. Step through each selectable topic on the left side of the interface and watch the associated animation/video.

What is Cancer? Cancer is cell replication gone terribly wrong. Our cells are replicating themselves all of the time. As with nearly all processes, cell replication is sometimes imperfect, and sometimes grossly so. Cancer is a multistage disease that goes through various cell transformations and sometimes long periods of latency in its progression. Cancer is not a state of being (that is, an invasive group of fast-growing cells) but a process, called carcinogenesis. The three main processes of cancer are growth, invasion and metastasis.

Most legitimate researchers, including Nobel prize winner Sir MacFarlane Burnet, know that in the normal body, tens of thousands of potential cancer cells appear every day. These defective, mutated cells are usually destroyed by the normal immune system and never cause a problem. Cancer only gets started when a failing immune system begins to allow abnormal cells to slip by without triggering an attack on them. Some cancer cells do not trigger the immune response at all because the internal DNA is not that different from your normal cells. Those mutated cells then begin the process of proliferation, having lost the ability to specialize. These “cancerous” cells also gain the advantage of losing the pre programmed process of cell death known as apoptosis.

Apoptosis is defined as; a genetically directed process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or removal of a suppressing agent or stimulus, and is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells —also called programmed cell death. Therefore, apoptosis represents a safeguard mechanism for an organism to rid itself of dangerously mutated cells. Mutations reducing the efficiency of apoptotic execution can – in consequence – favor the survival of cells carrying tumorigenic genetic lesions. Without being attacked by hunter killer cells, or having programmed cell death, these cancerous cells basically become “immortal” and can grow unchecked and unabated. In it’s most basic definition, cancer is runaway tissue growth.

Cancer isn’t just a single condition; it’s actually a complex collection of diseases that can arise in almost any tissue in the body. What characterizes full-blown cancer cells is that they’ve become decidedly anti-social, carrying on their activities without regard to the other cells and tissues around them. Most normal cells are monitored by a myriad of mechanisms that keep them working in cooperation with other cells. When damage prevents them from doing so, they fix themselves or die. Every cancer starts as a disruption of this normal activity. For example, most cells know it’s time to divide when they get signals from nearby cells or other parts of the body. Cancer cells, however, will divide whenever they please, regardless of how much they crowd their neighbors. They’ll also move to places they don’t belong, attract blood vessels to themselves, and stop obeying aging signals. In short, cancer cells misbehave, and their mischief gives rise to tumors.

Each cancer has its own unique pattern of bad behavior determined by the tissue in which it was formed, the mutations the cells have adopted, and the chemistry in an individual’s body. Because every cancer is unique, a treatment that works wonders for a leukemia patient, for example, might do little or nothing for a woman with breast cancer. Even patients who have the same kind of cancer will have different responses to the same therapy, because the way the cancer arises and plays out depends on unique cellular events and the patient’s individual genome.

What is the cause of cancer? There isn’t just one, not in any similar sense to the way one can consider a particular pathogen as the cause of a particular communicable disease. Cancer is absolutely muti-factorial. Cancer is reasonably best understood as an inherent vulnerability. We’re all born with a potential for cancer, because we are an organized collection of cells which replicate, and this process can go awry, sometimes disastrously. Virtually all organized creatures are subject to cancer. Some plants are vulnerable to metastasizing diseases comparable to cancer. The irritation of tissues influences the risk of mutant cell replication in an affected area. Lifestyle factors can influence cancer risk such as smoking, but cancer risk in itself is an inheritance we receive at birth. It’s part of being a mortal creature. It is your base risk. If there is a cause of cancer, it is nature.

This sequence shows an early step in the spread of a cancer (a process called metastasis). A breast cancer cell has traveled in the bloodstream and has arrived at the liver, where it stops because it is too big to keep moving through the tiny blood vessels to get to another organ. The cell appears bright because it has been labeled with a fluorescent dye to help identify it.

An early step in metastasis. This cancer cell has escaped from the bloodstream and is partly wrapped around the outside of a blood vessel. Because of this, it does not need to attract new blood vessels at this stage.

The first step in the growth of a new, metastatic cancer. This cancer is made up of two cells, which formed from the cell division of a single cell that had escaped out of the bloodstream. It still does not need angiogenesis at this stage, and it is growing next to a pre-existing blood vessel.

This shows a very small metastatic cancer, early in its development. This is a melanoma tumor, so it appears black. It is growing around a blood vessel, and you can see its three-dimensional shape as the microscope focuses up and down through it. This small tumor still does not need to attract new blood vessels to support its growth, because the blood vessel that it surrounds can support its growth at this size.

As tumors grow larger, they begin to develop the need for angiogenesis and must attract new blood vessels if they are to keep growing. This small melanoma cancer is beginning to show signs of blood vessel activity inside it, and these might be ‘angiogenic’ new blood vessels.

This melanoma tumor is larger, about half a millimeter wide, or roughly the size of a tiny grain of sand. By this stage, the tumor needs to continuously attract new vessels to keep on growing. The normal liver tissue (lighter color) shows normal, healthy blood flow, and the tumor (darker color) shows new, angiogenic blood vessels with irregular shapes and blood flow, especially visible in the higher magnification clip.

This melanoma tumor, also about a half a millimeter wide, is growing on the body cavity wall of a mouse. The black portion is the tumor and shows abnormal ‘angiogenic’ blood vessels, while the normal tissue (lighter color) has more normal blood flow.

This tumor, about a tenth of a millimeter wide and three-tenths of a millimeter long, is also growing on the body cavity wall. It has attracted new blood vessels to grow up to it from the normal muscle tissue below. When tumors get to be this size, they need continuous angiogenesis to keep on growing, otherwise their growth will stop.

This view, taken with a color video camera, shows normal, healthy blood vessels in mouse mammary (breast) tissue. The red-filled vessels are blood vessels, and the clear vessel (to the right of a large blood vessel) is a lymph vessel. These blood and lymph vessels show good flow and regular branching patterns, typical of normal, healthy organs.

This view shows a breast tumor growing in mouse breast tissue. The tumor appears green, because the cancer cells were labeled with a fluorescent dye, and the blood vessels appear black. These are new, angiogenic vessels, and their structure and blood flow look very irregular when compared to the regular patterns seen in normal, healthy tissue (as in the previous clip).

For the most part, every cell in your body has the same DNA in it, contained in 23 pairs of chromosomes, which must be copied with extraordinary accuracy each time the cell divides. Sometimes, though, there are mistakes, called mutations, in the DNA.

Surprisingly, most damage to the DNA happens through “normal” cellular metabolism. In addition to this normal rate of damage, our cells are constantly acquiring mutations in other ways as well, from ultraviolet rays in sunlight, exposure to environmental toxins, and the food we eat.

Other things can go wrong inside the cell:

Its machinery can stop working properly, creating problems replicating or dividing up DNA during cell division, or sometimes viral DNA can take up residence in the cell. Fortunately, we have lots of built-in mechanisms to correct these errors when they happen. Usually a cell with mutations will stop and fix its DNA; if it can’t, it will undergo apoptosis. But every now and then, a damaged cell slips through the repair checkpoint and the immune system’s surveillance system.

The more damage inflicted on the cell, the more likely it is to malfunction and potentially become precancerous. What happens then? Most mutations will kill a cell rather than give it super powers. But if the cell survives, it will pass its mutations along as it divides.

Mutations that affect DNA replication can give rise to new genetic changes as the cell divides. As these random changes accumulate, they can affect the cell’s behavior, bestowing upon it the qualities associated with cancer: uncontrolled growth, lack of response to signals, etc.

This proliferation of misbehaving and adaptation by cells is a microcosmic example of genetic variation and natural selection, a kind of malicious cellular evolution.